Administration of T Lymphocytes for Prevention of Relapse of Lymphomas
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02663297|
Recruitment Status : Recruiting
First Posted : January 26, 2016
Last Update Posted : January 29, 2019
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) administration.
In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes make up the chemical structure carrying the patient's genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells in this study makes a piece of an antibody called anti-CD30. This antibody floats around in the blood and can detect and stick to cancer cells called lymphoma cells because they have a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood part of it is now joined to the T cells. Only the part of the antibody that sticks to the lymphoma cells is attached to the T cells instead of the entire antibody. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown.
The purpose of this research study is to determine a safe dose of the ATLCAR.CD30 cells that can be given to subjects after undergoing an autologous transplant. This is the first step in determining whether giving ATLCAR.CD30 cells to others with lymphoma in the future will help them. The researchers also want to find out what side effects patients will have after they receive the ATLCAR.CD30 cells post-transplant. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on your cancer and how long they will survive in your body.
|Condition or disease||Intervention/treatment||Phase|
|Hodgkin Disease Lymphoma Lymphoma, Non-Hodgkin Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type||Drug: ATLCAR.CD30 cells||Phase 1|
Hide Detailed Description
- To determine the safety and tolerability and to estimate the MTD of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma at high risk for relapse
- To measure the survival of ATLCAR.CD30 in vivo
- To estimate PFS after infusion of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma at high risk for relapse
- To determine the overall survival after infusion of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma at high risk for relapse
- To measure patient-reported symptom, physical function, and health-related quality of life at baseline and over time in patients treated with ATLCAR.CD30 cells.
- Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) and CRS toxicity will be graded according to the toxicity scale outlined in 11.6 (Appendix F: CRS Toxicity Grading Scale and Management Guidelines). The MTD will be based on the rate of dose-limiting toxicity
Secondary (Clinical) Endpoint
- PFS is defined from day of ASCT to relapse (in subjects with a documented complete response after ASCT) or progression (in subjects with documented stable disease or partial response after ASCT), or death as a result of any cause as per the Revised Response Criteria for Malignant Lymphoma.
- Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to date of death
- Persistence of CAR.CD30 T cells in vivo will be determined by quantitative PCR and flow cytometry in peripheral blood samples.
- Patient reported symptoms will be measured using selected symptoms from the NCI PRO-CTCAE. Patient-reported physical function will be measured using the PROMIS Physical Function Score derived from the PROMIS Physical Function Short Form 20a v1.0. Patient-reported health-related quality of life will be measured using the PROMIS Global Health Score derived from the PROMIS Global Health Short Form v1.0-1.1.
Patients scheduled to undergo an autologous stem cell transplantation (ASCT) for treatment of lymphoma will be approached for consent to screening and potential enrollment into LCCC1524. Peripheral blood cells will be collected from consenting patients who meet eligibility for cell procurement for creation of ATLCAR.CD30 cells prior to ASCT. The ASCT, including mobilization and collection of PBSCs, administration of myeloablative therapy, reinfusion of PBSCs and supportive care following transplant will be as per routine standard of care, and not expected to be impacted by enrollment into LCCC1524. Post ASCT, patients who meet eligibility criteria for treatment will receive one infusion of ATLCAR.CD30 cells once there is evidence of hematologic recovery. Research personnel will keep track of any patients who undergo procurement but do not undergo treatment with ATLCAR.CD30 cells, and the reason for withholding treatment.
Peripheral blood, up to 300 mL total (in up to 3 collections) will be obtained for subjects for cell procurement. In patients with low (CD3 count as assayed by flow cytometry less than 200/μl) T-cell count in the peripheral blood, a leukopheresis may be performed to isolate sufficient T cells. The parameters for pheresis will be up to 2 blood volumes.
For pediatric patients (patients under 18 years of age), the total amount of blood drawn will not be more than 3 mL (less than 1 teaspoon per 2.2 lbs. that the child weighs.
ATLCAR.CD30 Cells Administration
Post ASCT, once the patient has started to experience hematologic recovery (defined as ANC ≥500 cells/mm3 for 3 consecutive days, AND platelet count ≥25 cells/mm3 without transfusion over the preceding 5 days, AND Hg ≥8g/dL without transfusion support over preceding 5 days), ATLCAR.CD30 cells will be admnistered. This will generally occur between 14 and 20 days following infusion of autologous stem cells following high-dose chemotherapy.
Duration of Therapy
Therapy in LCCC1524 involves just one infusion of ATLCAR.CD30 cells. Treatment with one infusion will be administered unless:
- Patient decides to withdraw from study treatment, OR
- General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.
Duration of Follow-Up
Patients will be followed for up to 15 years or until death, whichever occurs first. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) for Prevention of Relapse of CD30+ Lymphomas After High Dose Therapy and Autologous Stem Transplantation (ATLAS)|
|Actual Study Start Date :||July 15, 2016|
|Estimated Primary Completion Date :||September 2019|
|Estimated Study Completion Date :||September 2034|
Experimental: ATLCAR.CD30 cells
Three dose levels of ATLCAR.CD30 cells will be evaluated. Using the modified continual reassessment method (CRM), initial cohort of size two will be enrolled at each dose level after that subjects are enrolled one at a time until a minimum of 12 patients is treated. Each patient will receive one injection according to the dosing schedules listed below. Investigators will start with the lowest cell dose (2X10^7 cells/m^2) given to patients in one of our previous trials employing CAR-T cells including the CD28 costimulatory endodomain, and investigators will escalate the cell dose to the highest cell dose (2X10^8/m^2) given in the same trial.
Note: Initially, only adults will be enrolled during the dose escalation phase of the study. Once a dose level has been tested in at least 2 adults without the occurrence of dose limiting toxicities (DLTs), children may then be enrolled on that dose level according to the CRM.
Drug: ATLCAR.CD30 cells
Three dose levels will be evaluated:
Group One, 2x10^7 cells/m^2 (maximum dose 5x10^7 cells)
Group Two, 1x10^8 cells/m^2 (maximum dose 2.5x10^8 cells)
Group Three, 2x10^8 cells/m^2 (maximum dose 5x10^8 cells)
Other Name: CAR.CD30 T cells
- Number of participants with adverse events as a measure of safety and tolerability of escalating doses of autologous activated T lymphocytes [ Time Frame: 6 weeks ]Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) and cytokine release syndrome (CRS) toxicity will be graded according to the toxicity scale outlined in 11.6 (Appendix F: CRS Toxicity Grading Scale and Management Guidelines). The MTD will be based on the rate of dose-limiting toxicity
- To measure the survival of ATLCAR.CD30 in vivo [ Time Frame: 15 years ]Persistence of CAR.CD30 T cells in vivo will be determined by quantitative polymerase chain reaction (PCR) and flow cytometry in peripheral blood samples
- To estimate PFS after infusion of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma at high risk for relapse [ Time Frame: 15 years ]PFS is defined from day of ASCT to relapse (in subjects with a documented complete response after ASCT) or progression (in subjects with documented stable disease or partial response after ASCT), or death as a result of any cause as per the Revised Response Criteria for Malignant Lymphoma
- Determine the overall survival after infusion of ATLCAR.CD30 [ Time Frame: 15 years ]Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to date of death
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02663297
|Contact: Catherine Chengfirstname.lastname@example.org|
|Contact: Spencer Laingemail@example.com|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Catherine Cheng 919-445-4208 firstname.lastname@example.org|
|Contact: Spencer Laing 919-962-8618 email@example.com|
|Principal Investigator: Thomas Shea, MD|
|Wake Forest University||Recruiting|
|Winston-Salem, North Carolina, United States, 27157|
|Contact: Rakee Vaidya, M.B.B.S 336-716-2774 firstname.lastname@example.org|
|Principal Investigator: Rakee Vaidya, M.B.B.S|
|Principal Investigator:||Thomas Shea, MD||Director, Bone Marrow Transplant Program|